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Cyclodextrin mediated delivery of NF-κB and SRF siRNA reduces the invasion potential of prostate cancer cells in vitro

Gene Therapy volume 22, pages 802–810 (2015)Cite this article

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Abstract

Prostate cancer is the most common cancer in men of the western world. To date, no effective treatment exists for metastatic prostate cancer and consequently, there is an urgent need to develop new and improved therapeutics. In recent years, the therapeutic potential of RNA interference (RNAi) has been extensively explored in a wide range of diseases including prostate cancer using numerous gene delivery vectors. The aims of this study were to investigate the ability of a non-viral modified cyclodextrin (CD) vector to deliver siRNA to the highly metastatic PC-3 prostate cancer cell line, to quantify the resulting knockdown of the two target genes (RelA and SRF) and to study the effects of the silencing on metastasis. Data from a Matrigel in vitro invasion assay indicated that the silencing of the target genes achieved by the CD vector resulted in significant reductions (P=0.0001) in the metastatic potential of these cells. As the silencing of these target genes was shown not to have a negative impact on cell viability, we hypothesise that the mechanism of invasion inhibition is due, in part, to the significant reduction observed (P⩽0.0001) in the level of pro-inflammatory cytokine, MMP9, which is known to be implicated in the metastasis of prostate cancer.

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Acknowledgements

This work is supported by the Irish Cancer Society via a Research Scholarship to JCE (CRS12EVA) and a Project Grant to COD (PCI11ODR). We thank Bruno Godinho PhD for his technical assistance with the MSD analysis and Meenakshi Malhotra PhD, Amanda O’Neill PhD and Karen Hanrahan MSc for their help with the western blot experiments.

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Authors and Affiliations

  1. Pharmacodelivery Group, School of Pharmacy, University College Cork, Cork, Ireland

    J C Evans, J McCarthy & C M O’Driscoll

  2. Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland

    C Torres-Fuentes & J F Cryan

  3. Centre for Synthesis and Chemical Biology, Conway Institute, University College Dublin, Dublin, Ireland

    J Ogier & R Darcy

  4. UCD Conway Institute of Biomolecular and Biomedical Research, UCD School of Medicine and Medical Sciences, University College Dublin, Dublin, Ireland

    R W Watson

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  1. J C Evans
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Correspondence to C M O’Driscoll.

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Evans, J., McCarthy, J., Torres-Fuentes, C. et al. Cyclodextrin mediated delivery of NF-κB and SRF siRNA reduces the invasion potential of prostate cancer cells in vitro. Gene Ther 22, 802–810 (2015). https://doi.org/10.1038/gt.2015.50

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